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Demineralized bone matrix in bone repair: history and use.

ABSTRACT: Demineralized bone matrix (DBM) is an osteoconductive and osteoinductive commercial biomaterial and approved medical device used in bone defects with a long track record of clinical use in diverse forms. True to its name and as an acid-extracted organic matrix from human bone sources, DBM retains much of the proteinaceous components native to bone, with small amounts of calcium-based solids, inorganic phosphates and some trace cell debris. Many of DBM's proteinaceous components (e.g., growth factors) are known to be potent osteogenic agents. Commercially sourced as putty, paste, sheets and flexible pieces, DBM provides a degradable matrix facilitating endogenous release of these compounds to the bone wound sites where it is surgically placed to fill bone defects, inducing new bone formation and accelerating healing. Given DBM's long clinical track record and commercial accessibility in standard forms and sources, opportunities to further develop and validate DBM as a versatile bone biomaterial in orthopedic repair and regenerative medicine contexts are attractive.

SUBMITTER: Gruskin E

PROVIDER: S-EPMC7103314 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Demineralized bone matrix in bone repair: history and use.

Gruskin Elliott E Doll Bruce A BA Futrell F William FW Schmitz John P JP Hollinger Jeffrey O JO

Advanced drug delivery reviews 20120621 12

Demineralized bone matrix (DBM) is an osteoconductive and osteoinductive commercial biomaterial and approved medical device used in bone defects with a long track record of clinical use in diverse forms. True to its name and as an acid-extracted organic matrix from human bone sources, DBM retains much of the proteinaceous components native to bone, with small amounts of calcium-based solids, inorganic phosphates and some trace cell debris. Many of DBM's proteinaceous components (e.g., growth fac ...[more]

PMID: 22728914

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Project description:BackgroundDemineralized bone matrix is commonly used as a bone graft substitute, either alone or to supplement an osteoconductive material, because of its osteoinductive properties. The aging of the population has led to an increase in the number of prospective donors of demineralized bone matrix who have taken bisphosphonates to prevent osteoclast-mediated bone resorption. The aim of this study was to determine whether oral bisphosphonate usage affects the osteoinductivity of demineralized bone matrix from donors.MethodsSex-matched and age-matched pairs of samples were provided by four tissue banks (three or four pairs per bank). Demineralized bone matrix donors without bisphosphonate treatment had a mean age (and standard deviation) of 69.1 ± 2.5 years, and donors with bisphosphonate treatment had a mean age of 68.9 ± 2.0 years. Each pair included one donor known to have taken bisphosphonates and one who had not taken bisphosphonates. Demineralized bone matrix previously confirmed as osteoinductive was the positive control, and heat-inactivated demineralized bone matrix was the negative control. Demineralized bone matrix incubated with 1 mL of phosphate-buffered saline solution containing 0, 0.002, 2.0, or 2000 ng/mL of alendronate was also tested. Gelatin capsules containing 15 mg of demineralized bone matrix were implanted bilaterally in the gastrocnemius muscle of male nude mice (eight implants per group). The mice were killed thirty-five days after implantation, and hind limbs were recovered and processed for histological analysis. Osteoinductivity was measured with use of a qualitative score and by histomorphometry.ResultsNine of fifteen samples from donors who had had bisphosphonate treatment and ten of fifteen samples from patients who had not had bisphosphonate treatment were osteoinductive. Qualitative mean scores were comparable (1.7 ± 0.4 for those without bisphosphonates and 1.9 ± 0.7 for those with bisphosphonates). Osteoinductive demineralized bone matrix samples produced ossicles of comparable size, regardless of bisphosphonate usage. Histomorphometric measurements of the area of new bone formation and residual demineralized bone matrix were also comparable. The addition of alendronate to control demineralized bone matrix did not affect its osteoinductivity.ConclusionsDemineralized bone matrix samples from donors treated with bisphosphonates and donors not treated with bisphosphonates have the same ability to induce bone formation. However, it is not known if the quality of the new bone is affected, with subsequent consequences affecting bone remodeling.

Project description:ObjectivesDentin, the bulk material of the tooth, resemble the bone's chemical composition and is considered a valuable bone substitute. In the current study, we assessed the cytotoxicity and osteogenic potential of demineralized dentin matrix (DDM) in comparison to HA nanoparticles (n-HA) on bone marrow mesenchymal stem cells (BMMSCs) using a hydrogel formulation.Materials and methodsHuman extracted teeth were minced into particles and treated via chemical demineralization using ethylene diamine tetra-acetic acid solution (EDTA) to produce DDM particles. DDM and n-HA particles were added to the sodium alginate then, the combination was dripped into a 5% (w/v) calcium chloride solution to obtain DDM hydrogel (DDMH) or nano-hydroxyapatite hydrogel (NHH). The particles were evaluated by dynamic light scattering (DLS) and the hydrogels were evaluated via scanning electron microscope (SEM). BMMSCs were treated with different hydrogel concentrations (25%, 50%, 75% and neat/100%) and cell viability was evaluated using MTT assay after 72 h of culture. Collagen-I (COL-I) gene expression was studied with real-time quantitative polymerase chain reaction (RT-qPCR) after 3 weeks of culture and alkaline phosphatase (ALP) activity was assessed using enzyme-linked immune sorbent assay (ELISA) over 7th, 10th, 14th and 21st days of culture. BMMSCs seeded in a complete culture medium were used as controls. One-way ANOVA was utilized to measure the significant differences in the tested groups.ResultsDLS measurements revealed that DDM and n-HA particles had negative values of zeta potential. SEM micrographs showed a porous microstructure of the tested hydrogels. The viability results revealed that 100% concentrations of either DDMH or NHH were cytotoxic to BMMSCs after 72 h of culture. However, the cytotoxicity of 25% and 50% concentrations of DDMH were not statistically significant compared to the control group. RT-qPCR showed that COL-I gene expression was significantly upregulated in BMMSCs cultured with 50% DDMH compared to all other treated or control groups (P < 0.01). ELISA analysis revealed that ALP level was significantly increased in the groups treated with 50% DDMH compared to 50% NHH after 21 days in culture (P < 0.001).ConclusionThe injectable hydrogel containing demineralized dentin matrix was successfully formulated. DDMH has a porous structure and has been shown to provide a supporting matrix for the viability and differentiation of BMMSCs. A 50% concentration of DDMH was revealed to be not cytotoxic to BMMSCs and may have a great potential to promote bone formation ability.

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Demineralized bone matrix in bone repair: history and use.

Publications

Demineralized bone matrix in bone repair: history and use.

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